Three SNPs in chromosome 11q23.3 are independently associated with systemic lupus erythematosus in Asians

Hum Mol Genet. 2014 Jan 15;23(2):524-33. doi: 10.1093/hmg/ddt424. Epub 2013 Sep 2.

Abstract

Systemic lupus erythematosus (SLE) has a complex etiology and is affected by both genetic and environmental factors. Although more than 40 loci have shown robust association with SLE, the details of these loci, such as the independent contributors and the genes involved, are still unclear. In this study, we performed meta-analysis of two existing genome-wide association studies (GWASs) on Chinese Han populations from Hong Kong and Anhui, China, and followed the findings by further replication on three additional Chinese and Thailand cohorts with a total of 4254 cases and 6262 controls matched geographically and ethnically. We discovered multiple susceptibility variants for SLE in the 11q23.3 region, including variants in/near PHLDB1 (rs11603023, P(_combined) = 1.25E-08, OR = 1.20), DDX6 (rs638893, P(_combined) = 5.19E-07, OR = 1.22) and CXCR5 (rs10892301, P(_combined) = 2.51E-08, OR = 0.85). Genetic contributions from the newly identified variants were all independent of SNP rs4639966, whose association was reported from the previous GWAS. In addition, the three newly identified variants all showed independent association with the disease through modeling by both stepwise and conditional logistic regression. The presence of multiple independent variants in this region emphasizes its role in SLE susceptibility, and also hints the possibility that distinct biological mechanisms might be involved in the disease involving this genomic region.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Case-Control Studies
  • Chromosomes, Human, Pair 11*
  • DEAD-box RNA Helicases / genetics*
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Logistic Models
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / genetics*
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Proteins / genetics*
  • Receptors, CXCR5 / genetics*

Substances

  • CXCR5 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • PHLDB1 protein, human
  • Proto-Oncogene Proteins
  • Receptors, CXCR5
  • DDX6 protein, human
  • DEAD-box RNA Helicases